In this thesis, I have developed methods to systematically modify the core, shell, and surface of the protein microspheres. In addition, I have shown that the size of these spheres can be reduced from the micron scale to the nano scale. These modifications have thus improved the versatility and the applicability of the microspheres to a variety of applications. Modifications involving nanoparticles have resulted in the first class of optical contrast agents for optical coherence tomography (OCT). Modifications with receptor specific peptides have generated microspheres that can be targeted to tumor cells. And finally, modifications of the microspheres with nucleic acids have opened the door to new applications in gene therapy.